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Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach.
- Source :
-
European Archives of Psychiatry & Clinical Neuroscience . Apr2018, Vol. 268 Issue 3, p301-316. 16p. 4 Charts. - Publication Year :
- 2018
-
Abstract
- Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (<italic>TBCD</italic>) and rs4565946 (<italic>TPH2</italic>) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, <italic>SLC1A1</italic> in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (<italic>PICALM</italic>). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09401334
- Volume :
- 268
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- European Archives of Psychiatry & Clinical Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 128598040
- Full Text :
- https://doi.org/10.1007/s00406-017-0808-8